Rates of Spontaneous Mutation

Abstract

Rates of spontaneous mutation per genome as measured in the laboratory are remarkably similar within broad groups of organisms but differ strikingly among groups. Mutation rates in RNA viruses, whose genomes contain ca. 104 bases, are roughly 1 per genome per replication for lytic viruses and roughly 0.1 per genome per replication for retroviruses and a retrotransposon. Mutation rates in microbes with DNA-based chromosomes are close to 1/300 per genome per replication; in this group, therefore, rates per base pair vary inversely and hugely as genome sizes vary from 6 × 103 to 4 × 107 bases or base pairs. Mutation rates in higher eukaryotes are roughly 0.1–100 per genome per sexual generation but are currently indistinguishable from 1/300 per cell division per effective genome (which excludes the fraction of the genome in which most mutations are neutral). It is now possible to specify some of the evolutionary forces that shape these diverse mutation rates.

Lack of transgenerational effects of ionizing radiation exposure from the Chernobyl accident

“…Only recently has it been feasible to comprehensively investigate DNMs genome-wide at the population level in humans by whole-genome sequencing (WGS) of mother/ father/child trios. Recent reports of human DNMs characterized by WGS of trios estimate between 50 and 100 new mutations arise per individual per generation (2,(4)(5)(6)(7)(8), consistent with the population genetic estimate that the human mutation rate for single-nucleotide variants (SNVs) is approximately 1×10 −8 per site per generation (9,10). The strongest predictor of DNMs per individual is paternal age at conception (2)(3)(4)(5)(6)8) with an increase of 0.64-1.51 per one-year increase in paternal age (6,8,11) while a maternal effect of approximately 0.35 per one-year increase in age was observed (6,8,12).…”

Validation of high rates of nucleotide substitution in geminiviruses: phylogenetic evidence from East African cassava mosaic viruses

“…Although which substitutions are overrepresented may vary among geminiviruses, spontaneous oxidative mutations could be adding to the polymerase-induced mutation rate in all geminiviruses. This mechanism can help to explain the difference between the low estimated per base mutation rate of plant DNA polymerases (Drake et al, 1998) and the necessarily high per base mutation rate of geminiviruses.…”

Deciphering the Pathogenic Nature of Two de novo Sequence Variations in a Patient with Shprintzen-Goldberg Syndrome

“…Spontaneous mutations are predicted to be higher in eukaryotes [Drake et al, 1998], and there are various ways to determine spontaneous mutations [Foster, 2006]. As could be predicted, a single spontaneous mutation in a single gene such as SKI is likely to be approximately 10 -6 ; for 2 mutations to occur, the chance is about 10 -12.…”